rs2072744

Variant names:

• chrX-43740189-T-C
• rs2072744
• NM_000240.4:c.1107-492T>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_000240.4(MAOA):​c.1107-492T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.54 (12263 hom., 17508 hem., cov: 23)
  • Failed GnomAD Quality Control
• Consequence: MAOA NM_000240.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0680
• Publications: 9 publications found

Genes affected

MAOA (HGNC:6833): (monoamine oxidase A) This gene is one of two neighboring gene family members that encode mitochondrial enzymes which catalyze the oxidative deamination of amines, such as dopamine, norepinephrine, and serotonin. Mutation of this gene results in Brunner syndrome. This gene has also been associated with a variety of other psychiatric disorders, including antisocial behavior. Alternatively spliced transcript variants encoding multiple isoforms have been observed. [provided by RefSeq, Jul 2012]

MAOA Gene-Disease associations (from GenCC):

• Brunner syndrome

  Inheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, G2P, ClinGen, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAOA	NM_000240.4	c.1107-492T>C		intron_variant	Intron 10 of 14	ENST00000338702.4	NP_000231.1
MAOA	NM_001270458.2	c.708-492T>C		intron_variant	Intron 11 of 15		NP_001257387.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAOA	ENST00000338702.4	c.1107-492T>C		intron_variant	Intron 10 of 14	1	NM_000240.4	ENSP00000340684.3

Frequencies

GnomAD3 genomes AF: 0.537 AC: 59506 AN: 110736 Hom.: 12274 Cov.: 23

Gnomad AFR AF: 0.307

Gnomad AMI AF: 0.553

Gnomad AMR AF: 0.623

Gnomad ASJ AF: 0.627

Gnomad EAS AF: 0.425

Gnomad SAS AF: 0.355

Gnomad FIN AF: 0.592

Gnomad MID AF: 0.631

Gnomad NFE AF: 0.659

Gnomad OTH AF: 0.557

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.537 AC: 59502 AN: 110786 Hom.: 12263 Cov.: 23 AF XY: 0.530 AC XY: 17508 AN XY: 33058

African (AFR) AF: 0.307 AC: 9406 AN: 30606

American (AMR) AF: 0.622 AC: 6463 AN: 10386

Ashkenazi Jewish (ASJ) AF: 0.627 AC: 1642 AN: 2617

East Asian (EAS) AF: 0.425 AC: 1486 AN: 3500

South Asian (SAS) AF: 0.356 AC: 953 AN: 2677

European-Finnish (FIN) AF: 0.592 AC: 3449 AN: 5824

Middle Eastern (MID) AF: 0.636 AC: 136 AN: 214

European-Non Finnish (NFE) AF: 0.659 AC: 34755 AN: 52778

Other (OTH) AF: 0.556 AC: 842 AN: 1515

Alfa AF: 0.591 Hom.: 4511

Bravo AF: 0.531

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.4
DANN	Benign	0.85
PhyloP100		-0.068
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2072744; hg19: chrX-43599436;